Historical and More Common Nongenetic Movement Disorders From Asia

Nongenetic movement disorders are common throughout the world. The movement disorders encountered may vary depending on the prevalence of certain disorders across various geographical regions. In this paper, we review historical and more common nongenetic movement disorders in Asia. The underlying causes of these movement disorders are diverse and include, among others, nutritional deficiencies, toxic and metabolic causes, and cultural Latah syndrome, contributed by geographical, economic, and cultural differences across Asia. The industrial revolution in Japan and Korea has led to diseases related to environmental toxin poisoning, such as Minamata disease and β-fluoroethyl acetate-associated cerebellar degeneration, respectively, while religious dietary restriction in the Indian subcontinent has led to infantile tremor syndrome related to vitamin B12 deficiency. In this review, we identify the salient features and key contributing factors in the development of these disorders.

Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution

Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.

Precision medicine in Parkinson′s disease: current status and future prospects / 中华神经科杂志

Parkinson′s disease is a common neurodegenerative disease with high clinical heterogeneity. With the development of precision medicine, numerous researches have been conducted on the pathological mechanism, clinical classification, diagnosis and treatment of Parkinson′s disease through multi-omics, bioformatics and molecular imaging. This article will elaborate the current practice and future research directions of precision medicine in the diagnosis and treatment of Parkinson′s disease.

Advances in the Diagnosis and Treatment of Multiple System Atrophy / 罕见病研究

Multiple system atrophy (MSA) is a rare and rapidly-progressive neurodegenerative disorder, characterized by the combination of dysautonomia, poor levodopa responsive parkinsonism, cerebellar ataxia, and pyramidal tract signs. Insidious onset, clinical heterogeneity and progression of the disease complicate the difficulty of early diagnosis and challenge, the development of neuroprotective drugs. In order to improve the knowledge of diagnosis and treatment of the disease, this paper reviews advances in its diagnostic criteria, biomarkers of early diagnosis and management of the disease.

Advances of cognitive impairment in amyotrophic lateral sclerosis / 中华神经科杂志

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor deficits. In recent years, cognitive impairment in ALS has been widely concerned, and the concept of ALS-frontotemporal dementia spectrum has been commonly recognized and well-established. With the development of neuropsychology, neuroimaging, neurophysiology, neuropathology and neurogenetics, advances have been made in the diagnosis and pathophysiological mechanism of cognitive impairment in ALS. The most recent advances of cognitive impairment in ALS were reviewed.

Lysosomal trafficking regulator gene c.421C>T homozygous mutation causes adult Chediak- Higashi syndrome: one case report / 中华神经科杂志

The mutation of lysosomal trafficking regulator (LYST) gene and the clinical data of an adult patient who showed an abnormal gait with Chediak-Higashi syndrome were analyzed retrospectively. The whole exon sequencing was applied, and Sanger sequencing was used to verify the results. All members of the family were genetically verified for the same mutation site. The sequencing revealed the presence of c.421C>T(p.Arg141 *) mutation in LYST gene in the proband, which was inherited from his parents. The mutation was found in the homozygous state for the proband, both his parents being heterozygous for the same mutation. This mutation type was not reported in the human gene mutation database. According to the American Society of Medical Genetics and Genomic Society′s guide to the interpretation of genetic variation, the mutation of c.421C>T was identified to be pathogenic.

Advances of motor unit number estimation and motor unit number index in amyotrophic lateral sclerosis / 中华神经科杂志

Amyotrophic lateral sclerosis (ALS) is a rapid progressive neurodegenerative disease, characterized by the degeneration of both upper and lower motor neurons. The progressive motor unit loss due to lower motor neuron damage is one of the most important pathological process in ALS. However, there are lack of specific biomarkers for early diagnosis and progression monitoring of ALS. The relevant electrophysiologic techniques which quantify the number of motor unit have been developed rapidly in recent years. Among them, the motor unit number estimation (MUNE) and the motor unit number index (MUNIX) have been widely applied to quantify motor unit number loss in ALS. The most recent advances of MUNE and MUNIX in ALS were reviewed.

Advance in research on biomarkers for amyotrophic lateral sclerosis / 中华医学遗传学杂志

Amyotrophic lateral sclerosis (ALS) is a relentless, progressive, and presently incurable neurodegenerative disease. Its drug development has been hampered by the lack of effective biomarkers for early diagnosis, progression and prognosis. Recently, significant progress has been made for the identification of body fluid biomarkers for ALS, which conferred both theoretical and practical feasibility for the early diagnosis and progression monitoring. Meanwhile, it also facilitated identification of genes and/or pathways for the pathogenesis of ALS. This review summarized biomarkers identified from cerebrospinal fluid, blood and urine of ALS patients and their clinical implications.

Intellectual disability due to heterozygous c.40C>T variant of TRIP12 gene in a patient / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a patient with intellectual disability.@*METHODS@#Whole exome sequencing and Sanger sequencing were carried out for the patient. The result was verified in her family.@*RESULTS@#DNA sequencing revealed that the patient has carried a heterozygous nonsense c.40C>T (p.Arg14X) variant of the TRIP12 gene, which was de novo in origin. The variant was unrecorded in the Human Gene Mutation Database. Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+ PS2+ PP3).@*CONCLUSION@#The patient was diagnosed with autosomal dominant intellectual disability due to heterozygous c.40C>T variant of the TRIP12 gene.

Research progress of neurofilament light chain in the parkinsonism / 中华神经科杂志

Neurofilament light chain (NfL), a sensitive biomarker of axonal damage, was found increasing in several neurological diseases. Parkinsonism is a group of clinical syndromes characterized by cardinal symptoms of bradykinesia, rigidity, and tremor, including Parkinson′s disease (PD) and parkinsonism plus syndrome (PPS). It is difficult in the diagnosis and differential diagnosis of PD and PPS, especially in the early stage. Evidence suggests that NfL in the cerebrospinal fluid and blood is a promising biomarker for the differential diagnosis of PD and PPS. This article reviewed and summarized the research progress of value of NfL in PD and PPS, and proposed future research directions.

Summary of the 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease / 中华神经科杂志

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

Progress in gene diagnosis of amyotrophic lateral sclerosis / 中华神经科杂志

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease,for which early diagnosis is still very difficult up to now.With more and more ALS pathogenic and risk genes discovered,and especially the application of clinical trials of gene therapy in ALS,the genetic diagnosis becomes far more essential in ALS clinical practice.This presentation is a general introduction to the advantages and disadvantages of the commonly used gene detection methods,the key features of the pathogenic genes,the relationship between genotype and phenotype and the strategy of risk gene detection.The most common causative gene in Chinese ALS patients is superoxide dismutase (SOD1) gene,while in the Caucasian population is chromosome 9 open reading frame 72 (C9ORF72) gene.Familial ALS should be recommended for screening of ALS pathogenic gene panels.If negative,whole exome or genome sequencing is recommended to locate new pathogenic genes.The SOD1 and C9ORF72 should be routinely screened no matter in familial or sporadic form of ALS.In addition,if the patient has a special clinical phenotype,such as rapid or slow progression,cognitive impairment or extrapyramidal symptoms,genetic detection will be of great value for the diagnosis.

Progress in gene diagnosis of amyotrophic lateral sclerosis / 中华神经科杂志

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, for which early diagnosis is still very difficult up to now. With more and more ALS pathogenic and risk genes discovered, and especially the application of clinical trials of gene therapy in ALS, the genetic diagnosis becomes far more essential in ALS clinical practice. This presentation is a general introduction to the advantages and disadvantages of the commonly used gene detection methods, the key features of the pathogenic genes, the relationship between genotype and phenotype and the strategy of risk gene detection. The most common causative gene in Chinese ALS patients is superoxide dismutase (SOD1) gene, while in the Caucasian population is chromosome 9 open reading frame 72 (C9ORF72) gene. Familial ALS should be recommended for screening of ALS pathogenic gene panels. If negative, whole exome or genome sequencing is recommended to locate new pathogenic genes. The SOD1 and C9ORF72 should be routinely screened no matter in familial or sporadic form of ALS. In addition, if the patient has a special clinical phenotype, such as rapid or slow progression, cognitive impairment or extrapyramidal symptoms, genetic detection will be of great value for the diagnosis.

Summary of the Twenty-ninth International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease / 中华神经科杂志

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.

Summary of the Twenty?ninth International Symposium on Amyotrophic Lateral Sclerosis?Motor Neuron Disease / 中华神经科杂志

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)?Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.

Identification of compound heterozygous mutations of SACS gene in two patients from a pedigree with spastic ataxia of Charlevoix-Saguenay / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of the spastic ataxia of Charlevoix-Saguenay (SACS) gene in a pedigree affected with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples of the proband and her family members. All exons and flanking sequences of the SACS gene were analyzed by high-throughput sequencing. Suspected mutations were verified with Sanger sequencing.</p><p><b>RESULTS</b>Next generation sequencing revealed novel compound heterozygous mutations of the SACS gene, namely c.13085T to G (p.I4362R) and c.5236dupA (p.T1746fs), in the proband, which were respectively derived from her parents. The mutations were confirmed by Sanger sequencing.</p><p><b>CONCLUSION</b>The c.5236dupA (p.T1746fs) and c.13085T to G (p.I4362R) mutations of the SACS gene probably underlie the ocular symptoms and hearing loss in the proband.</p>

Roles of exosomes in Parkinson's disease and amyotrophic lateral sclerosis / 中华医学遗传学杂志

Exosomes, as a kind of extracellular vesicles generated by inward budding of the endosomes to form multi-vesicular bodies (MVBs), are secreted into the extracellular milieu and the systemic circulation thereafter. By endocytosis, direct fusion or receptor-ligand interactions, exosomes can interact with receptor cells and involve in various pathophysiological processes. Accumulating evidence have indicated that exosomes may play crucial roles in the pathogenesis of many neurodegenerative diseases including Parkinson's disease (PD), Huntington's disease (HD), Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS). In this paper, the roles of exosomes in the pathogenesis, diagnosis and treatment of PD and ALS are reviewed.

Summary of the Twenty-eighth International Conference on Amyotrophic Lateral Sclerosis-Motor Neuron Disease / 中华神经科杂志

The 28th International Conference on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Boston from December 8 to 10, 2017. The conference covered 23 topics, 102 special topics and 446 papers. This article briefly introduces some topics of the conference, involving basic research, clinical research and clinical trials. Among these, basic studies include genetics, cell biology and pathology, and superoxide dismutase1 gene ALS related pathology; clinical studies include the progression of ALS disease, cognitive behavioral disorders, and biological markers.

Safety and efficacy of botulinum toxin type A made in China for treatment of post-stroke upper limb spasticity: a randomized double-blind controlled trial / 中华神经科杂志

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Parkinson's disease and nucleolar stress / 中华医学遗传学杂志

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized mainly by motor dysfunction resulting in bradykinesia, rigidity, tremor, gait impairment, and postural instability. The classic pathogenic feature of PD is preferential loss of dopaminergic neurons in the substantia nigra. Downregulation of rRNA transcription is one of major mechanisms to maintain cellular homeostasis under stress conditions. Nucleolar stress has emerged as a component of the degenerative process caused by impaired rRNA transcription and altered nucleolar integrity. Recent study has indicated that the response to stress conditions and quality control mechanisms are impaired in PD, and that metabolic stress may be a trigger mechanism for PD. This review aims to present evidence for a role of nucleolar stress in PD and has summarized mechanisms by which nucleolar stress may play a role in the progression of PD.